Method and equipment for continuous and selective inclusion separation

ABSTRACT

In a reaction system having at least two liquid-liquid interfaces between an organic phase of raw material containing a compound(s) to be separated and an aqueous phase of an aqueous solution of inclusion-complexing agent and between that aqueous phase and an organic phase(s) of extraction solvent(s), the compound(s) to be separated is entrapped into the aqueous phase through formation of an inclusion complex(es) of the inclusion-complexing agent with the compound(s), while the compound(s) is entrapped into the organic phase(s) of extraction solvent(s) through dissociation of said inclusion complex(es). The foregoing operation is performed using, for example, a squarish U-shaped tube or an H-shaped tube with bottom plates. Preferred examples of inclusion-complexing agent include highly water-soluble branched cyclodextrins.

This application is a 371 of PCT/JP00/09073, filed Dec. 21, 2000, whichclaims foreign priority benefit under 35 U.S.C. § 119 of the JapanesePatent Application No. 2000-59431 filed Mar. 3, 2000.

TECHNICAL FIELD

The present invention relates to a method of effectively separating avariety of compound(s) as an object(s) of separation useful as astarting material(s) of chemical syntheses and/or the like, and aseparator for use therein. Raw materials that can be subjected to themethod of the present invention are a wide variety of raw materials,examples of which include disubstituted benzene isomer mixtures such asxylene isomer mixtures, trisubstituted benzene isomer mixtures such astrimethylbenzene isomer mixtures, methylquinoline isomer mixtures,substituted naphthalene isomer mixtures such as methylnaphthalene isomermixtures and dimethylnaphthalene isomer mixtures, and optical isomermixtures of pinene, limonene, menthol, mandelic acid esters, etc.

BACKGROUND ART

Separation of compounds as objects of separation from raw materials asmentioned above is difficult or impossible by a customary distillationor crystallization method, so that special separation methods have beeninvented for and applied to respective raw materials.

The present inventors and the like had already discovered and patentedmethods according to which compounds as mentioned above can be highlyselectively separated using either an aqueous solution of highlywater-soluble substituted cyclodextrin such as branched cyclodextrin oran aqueous alkaline solution of unsubstituted cyclodextrin throughformation of inclusion complexes and subsequent liquid-liquidextraction. An organic compound(s) as an object(s) of separationentrapped in an aqueous solution of a cyclodextrin is contacted with anorganic solvent such as diethyl ether, or heated at a temperature of atleast 60° C., whereby the compound(s) can be dissociated from thecyclodextrin and recovered. However, a continuous process of treatmentsranging from entrapment of a compound(s) as an object(s) of separationin an aqueous solution of cyclodextrin to recovery thereof cannot easilybe established. This is not limited to a case where a cyclodextrin isused as one kind of inclusion-complexing agent.

Accordingly, an object of this invention is to provide a continuous andselective method of entrapping a compound(s) as an object(s) ofseparation into an aqueous phase made of an aqueous solution ofinclusion-complexing agent, and dissociating and recovering theentrapped compound(s) from the inclusion-complexing agent. Incidentally,the term “selective” used herein refers to a selectivity with whichthere can be attained an improvement in the purity of a compound as anobject of separation, which is sufficient enough to provide apossibility of developing an industrially useful process.

DISCLOSURE OF THE INVENTION

The present invention provides a continuous and selective inclusionseparation method characterized in that, in a reaction system having atleast two liquid-liquid interfaces between an organic phase of rawmaterial containing a compound(s) to be separated and an aqueous phaseof an aqueous solution of inclusion-complexing agent and between thataqueous phase and an organic phase(s) of extraction solvent(s), thecompound(s) to be separated is entrapped into the aqueous phase throughformation of an inclusion complex(es) of the inclusion-complexing agentwith the compound(s), while the compound(s) is entrapped into theorganic phase(s) of extraction solvent(s) through dissociation of theinclusion complex(es); and an inclusion separator characterized bycomprising a reaction vessel constructed so as to allow an aqueous phaseof an aqueous solution of inclusion-complexing agent to formliquid-liquid interfaces with at least two organic phases that are anorganic phase of raw material containing a compound(s) to be separatedand an organic phase(s) of extraction solvent(s), and stirring means forstirring at least neighborhoods of the respective liquid-liquidinterfaces. Incidentally, the reaction vessel may be provided with aheating and/or cooling means and/or pipings for feeding and/orwithdrawing the aqueous solution of inclusion-complexing agent, the rawmaterial and the extraction solvent(s) if necessary.

According to the present invention, a wide variety of raw material,examples of which include disubstituted benzene isomer mixtures such asxylene isomer mixtures, trisubstituted benzene isomer mixtures such astrimethylbenzene isomer mixtures, methylquinoline isomer mixtures,substituted naphthalene isomer mixtures such as methylnaphthalene isomermixtures and dimethylnaphthalene isomer mixtures, and optical isomermixtures of pinene, limonene, menthol, mandelic acid esters, etc., maybe contacted with an aqueous phase of an aqueous solution of, e.g.,highly water-soluble cyclodextrin such as a branched cyclodextrin as aninclusion-complexing agent to form at least an inclusion complex of thecyclodextrin with a compound contained in the raw material and to beseparated, while in parallel the aqueous phase is contacted with a widevariety of extraction solvent such as heptane to dissociate theinclusion complex, whereby the included compound can be recovered in theorganic phase of extraction solvent.

In the present invention, one liquid-liquid interface of the aqueousphase of the aqueous solution of inclusion-complexing agent such as acyclodextrin is an interface with the organic phase of raw materialcontaining a compound(s) to be separated, so that inclusion complexes ofinclusion-complexing agent with compounds in the organic phase of raw amaterial may be yielded toward their formation in accordance withcomplex formation constants thereof to selectively entrap in the aqueousphase a at compound to be separated. And other liquid-liquidinterface(s) of the aqueous phase is an interface(s) with an organicphase(s) of extraction solvent(s), so that the compound(s) entrapped inthe aqueous phase and to be separated can be dissociated to be extractedin the organic phase(s) of extraction solvent(s). The foregoingoperation can be performed using a reaction vessel, examples of whichinclude a U-shaped tube that may be squarish as shown in FIGS. 1 to 3and an H-shaped tube with bottom plates (hereinafter referred to simplyas an “H-shaped tube” ) as shown in FIGS. 4 to 6 to which the reactionvessel is not limited. Various altered reaction vessels are usable aswill be described later.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a conceptual cross-sectional view illustrating an example ofreaction vessel in the basic inclusion separator of the presentinvention that may be used in the method of the present invention.

FIG. 2 is a conceptual schematic cross-sectional view of an inclusionseparator used in Examples 12 and 28.

FIG. 3 is a conceptual schematic cross-sectional view of an inclusionseparator used in Examples 1 to 9, 11, 13 to 27, and 29 to 38.

FIG. 4 is a conceptual cross-sectional view illustrating another exampleof reaction vessel in the basic inclusion separator of the presentinvention that may be used in the method of the present invention, andshowing a state thereof wherein use is made of a raw material higher inspecific gravity than an aqueous phase and an extraction solvent lowerin specific gravity than the aqueous phase.

FIG. 5 is a conceptual cross-sectional view illustrating another exampleof reaction vessel in the basic inclusion separator of the presentinvention that may be used in the method of the present invention, andshowing a state thereof wherein use is made of a raw material lower inspecific gravity than an aqueous phase and an extraction solvent higherin specific gravity than the aqueous phase.

FIG. 6 is a conceptual cross-sectional view illustrating another exampleof reaction vessel in the basic inclusion separator of the presentinvention that may be used in the method of the present invention, andshowing a state thereof wherein use is made of a raw material and anextraction solvent both higher in specific gravity than an aqueousphase.

EXPLANATION OF SYMBOLS

-   1, 11, 21 . . . U-shaped tube, 31, 41, 51 . . . H-shaped tube,-   2, 22, 32, 42, 52 . . . diaphragm (not an indispensable element),-   3, 13, 23, 33, 43, 53 . . . aqueous (cyclodextrin) phase,-   4, 14, 24, 34, 44, 54 . . . organic phase of raw material,-   5, 15, 25, 35, 45, 55 . . . organic phase of extraction solvent.

MODES FOR CARRYING OUT THE INVENTION

Modes for carrying out this invention will now be described, but shouldnot be construed as limiting the scope of the invention. The followingdescription will be made with priority given to cases wherecyclodextrins are used as inclusion-complexing agents. However, it goeswithout saying that this invention is not limited to these cases inlight of the principle of the invention.

When the specific gravity of an organic phase of raw material like axylene mixture is considerably lower than that of an aqueous phase of anaqueous solution of cyclodextrin (hereinafter often referred to brieflyas an “aqueous cyclodextrin phase”), the organic phase of raw materialand an organic phase of extraction solvent may be respectively stirredtogether with the aqueous cyclodextrin phase in a U-shaped tube, wherebyinclusion complexation and dissociation-extraction can be effected withimproved contact efficiencies. On the other hand, when the specificgravity of the organic phase of raw material is not so lower than orslightly higher than that of the aqueous cyclodextrin phase, the organicphase of raw material is dispersed in or put under the aqueouscyclodextrin phase. When the organic phase of raw material is dissolvedinto the organic phase of extraction solvent, selective separation isnot effected as a matter of course. In this case, the aqueous phaseexisting between the organic phase of raw material containing acompound(s) to be separated and the organic phase of extraction solventmay be partitioned with a diaphragm permeable to the aqueous solutionbut hardly permeable to oily droplets to prevent the organic phase ofraw material dispersed in the aqueous cyclodextrin phase from migratinginto the organic phase of extraction solvent. Examples of the diaphragminclude filter paper, filter cloth, nonwoven fabric, net and textilemade of fibers of a material, examples of which include cellulose andderivatives thereof, rayon, hairy materials such as wool, silk,plastics, glass, silica, metals, etc.; porous plastic membranes; porousrigid plastic materials formed by sintering a plastic material; ceramicfilters formed by sintering ceramic fibers; and sintered stainlessfilters formed by sintering stainless steel fibers; provided that theymay optionally be treated so as to become oil-repellent. Apart from theforegoing case, use of the diaphragm can further improve the contactefficiencies because the organic phase of raw material and the organicphase of extraction solvent can be vigorously stirred together with theaqueous cyclodextrin phase, whereby the rates and efficiencies ofinclusion complexation and dissociation-extraction can be enhanced.After withdrawal of the organic phase of extraction solvent and additionof fresh extraction solvent, stirring and extraction may also becontinued afresh. Incidentally, where the specific gravity of rawmaterial and/or extraction solvent is higher than that of the aqueouscyclodextrin phase, the H-shaped tube as will be detailed later mayadvantageously be used. Where the specific gravity of the aqueouscyclodextrin phase is between those of the organic phases of rawmaterial and extraction solvent, an I-shaped tube with a bottom platemay also advantageously be used as the reaction vessel.

At least part of a solution as the organic phase of extraction solventcontaining a compound extracted thereinto as an object of separation mayadvantageously be withdrawn and distilled to concentrate the compound,and the organic solvent separated by distillation may be returned backto the reaction system and reused as the extraction solvent (see Example27). In this case, the efficiency of extraction can be enhanced becausethe extraction solvent is refreshed.

The foregoing inclusion complexation and dissociation-extractionoperation is performed preferably in the range of 0 to 50° C., morepreferably 5 to 40° C., further preferably 10 to 25° C.

Any aqueous phase of cyclodextrin will suffice insofar as it does notyield a solid substance when the cyclodextrin forms any inclusioncomplexes thereof with any organic compounds to be separated. Needlessto say, highly water-soluble substituted cyclodextrins such as branchedcyclodextrins can be used in the present invention. Even unmodifiedcyclodextrins may be used in the operation of the present invention ifthey are used in the form of an aqueous solution mixed with sodiumhydroxide, potassium hydroxide or the like for enhancing the watersolubilities thereof and hence enhancing the water solubilities of theresulting inclusion complexes without formation of any solid substance.

Examples of substituted cyclodextrins usable as inclusion-complexingagents in the present invention include substituted cyclodextrins suchas α-, β- or γ-cyclodextrin with at least one hydroxyl group thereofhaving its hydrogen atom substituted with at least one selected fromamong a glucosyl group, a maltosyl group, maltooligosaccharide residues,a methyl group, a hydroxyethyl group, hydroxypropyl groups, a sulfonicgroup, alkylenesulfonic groups, and carboxyalkyl groups. Herein, theterm “sulfonic group” is intended to encompass not only a group in thefree acid form but also groups in a salt form of sodium, potassium,ammonium, lower amine, ethanolamine or the like. The “carboxyl moiety”of “carboxyalkyl group” is intended to have the same meaning as the“sulfonic group.” The alkylene moiety of alkylenesulfonic group may beeither linear or branched, and is preferably 1 to 5 in the number ofcarbon atoms. The alkyl moiety of carboxyalkyl group may be eitherlinear or branched, and is preferably 1 to 5 in the number of carbonatoms. Preferred specific examples of usable cyclodextrins includemonoglucosyl-α-cyclodextrin, diglucosyl-α-cyclodextrin,triglucosyl-α-cyclodextrin, and mixtures thereof;monomaltosyl-α-cyclodextrin, dimaltosyl-α-cyclodextrin,trimaltosyl-α-cyclodextrin, and mixtures thereof;monoglucosyl-β-cyclodextrin, diglucosyl-β-cyclodextrin,triglucosyl-β-cyclodextrin, and mixtures thereof;monomaltosyl-β-cyclodextrin, dimaltosyl-β-cyclodextrin,trimaltosyl-β-cyclodextrin, and mixtures thereof;2,6-dimethyl-α-cyclodextrin; and 2,6-dimethyl-β-cyclodextrin.

The suitable cyclodextrin concentration is preferably 5 to 50 wt. %,further preferably 5 to 30 wt. %, based on the aqueous solution.

Examples of raw materials that can be subjected to selective separationwith the aid of a cyclodextrin include indole-containing mixtures(Japanese Patent Laid-Open No. 2-200671); disubstituted benzene isomermixtures such as xylene isomer mixtures, dichlorobenzene isomermixtures, nitrotoluene isomer mixtures, and chlorobenzotrifluorideisomer mixtures (Japanese Patent Laid-Open Nos. 3-184925 and 6-287149);trisubstituted benzene isomer mixtures such as trimethylbenzene isomermixtures, trichlorobenzene isomer mixtures, dimethylnitrobenzene isomermixtures, chloronitrotoluene isomer mixtures, dinitrotoluene isomermixtures, and xylenol isomer mixtures (Japanese Patent Laid-Open No.6-87765); 2-methylquinoline-containing hydrocarbon oils (Japanese PatentLaid-Open No. 2-255658); 7-methylquinoline-containing mixtures (JapanesePatent Laid-Open No. 4-321668); 2,6-diisopropylnaphthalene-containingmixtures (Japanese Patent Laid-Open Nos. 2-204419 and 2-209818);2-methylnaphthalene-containing mixtures (Japanese Patent Laid-Open No.2-255630); 2,6-dimethylnaphthalene-containing mixtures (Japanese PatentLaid-Open No. 6-116179); and optical isomer mixtures of pinene,limonene, menthol, mandelic acid esters, etc. Incidentally, in the caseof raw materials having a determined composition like mixed xylene, thepurity of a given compound in the residual organic phase of raw materialafter subjected to the method of the present invention is improved, sothat the residual organic phase of raw material may be repeatedlysubjected as raw material to the method of the present invention,whereby that purity can be improved to a desired level.

The amount of the organic phase of raw material containing a compound tobe separated is preferably such that the molar ratio of the compound toa cyclodextrin in the aqueous cyclodextrin phase is at least one. Wherethe raw material is a solid substance, it can be subjected in the formof a solution to separation after it is dissolved in a suitable organicsolvent hardly capable of being included in the cyclodextrin.

Organic solvents hardly soluble in water and hardly capable of formingan inclusion complex with a cyclodextrin are preferred as the organicsolvent for use in dissociating and extracting a compound entrapped inthe aqueous cyclodextrin phase from the cyclodextrin. Examples of suchorganic solvents include ethers such as diethyl ether, diisopropylether, and diisoamyl ether; hydrocarbons such as liquefied propane gas,L P G, liquefied butane gas, pentanes, hexanes, heptanes, andmesitylene; and halogenated hydrocarbons such as dichloromethane.Incidentally, in the case of an extraction solvent highly volatile witha boiling point of at least ordinary temperature and comparativelyeasily soluble in the aqueous solution of cyclodextrin like diethylether, it is preferred to repeat at suitable time intervals theprocedure of effecting extraction by stirring for a period of a fewseconds to several tens of seconds after addition of the extractionsolvent and then recovering the resulting organic solvent layer. In thiscase, as the extraction solvent in continuing the operation afterrecovery of the solvent layer, either virgin solvent may be replenished,or the solvent separated from the compound(s) as the object(s) ofseparation through distillation or the like of the solvent layer may bereused.

When a compound entrapped in the aqueous cyclodextrin phase hardlymigrates into the organic phase of extraction solvent or takes time forsuch migration, a saturating amount of a salt such as sodium chloride,potassium chloride or sodium sulfate may be dissolved in the aqueouscyclodextrin phase to facilitate migration of the included compound intothe organic phase of extraction solvent. This is believed to be sobecause the solubility of the compound entrapped in the aqueous phase islowered due to a salting-out effect.

Distillation may be used for separating the extracted organic compoundfrom the organic phase of extraction solvent. The organic phase ofextraction solvent wherein the compound to be separated is extracted istransferred to a distillation unit, wherein the compound to be separatedis concentrated. The extraction solvent separated by distillation may berepeatedly used for extraction. This can reduce the consumption of theextraction solvent.

When a low-boiling solvent boiling below ordinary temperature, e.g.,liquefied petroleum gas (LPG), liquefied propane gas or liquefied butanegas, is used as the extraction solvent, a raw material containing acompound(s) to be separated therefrom and an aqueous solution ofinclusion-complexing agent are placed in a reaction vessel such as aU-shaped tube or an H-shaped tube in an inclusion separator providedwith a pressurizing means, e.g., an apparatus having a reaction vesselplaced in an autoclave, and the low-boiling solvent is then placed inthe reaction vessel under pressure, followed by stirring to perform aseparation operation. After the separation operation, the separator isdepressurized to recover the vapor of the low-boiling solvent. Duringthe course of depressurization, heat being generated during liquefactionof the low-boiling solvent vapor through pressurization may be utilizedas an (ancillary) means for preventing temperature drop of the organicphase and the aqueous phase in the reaction vessel in keeping withevaporation of the low-boiling solvent (means particularly forpreventing the aqueous phase from freezing). The liquefied low-boilingsolvent can be reused as the extraction solvent. The extracted organiccompound(s) remaining in the reaction vessel is recovered.Alternatively, the organic phase after the extraction operation may befirst withdrawn from the reaction vessel into a pressure vessel fromwhich the low-boiling solvent vapor is recovered, instead of directrecovery of the low-boiling solvent vapor from the reaction vessel. Inthis case as well, heat being generated during pressurization andliquefaction of the low-boiling solvent vapor may of course be used asan (ancillary) means for preventing temperature drop of the residualorganic phase(s) and the aqueous phase. Advantages of using alow-boiling solvent boiling below ordinary temperature lie in that agreat difference in boiling point between a compound as an object ofseparation like axylene isomer and an extraction solvent hardly allowsthe low-boiling solvent to mix in the separated compound, and in that alarge-scale and elaborate distillation apparatus may be dispensed within performing an industrial separation process according to the presentinvention.

Examples of other inclusion-complexing agents include water-solublecyclophanes (Kiichi Takemoto, Mikiji Miyata & Keiichi Kimura, “InclusionCompounds—from Basics to Future Technologies—,” Edition 1, published byTokyo Kagaku Dozin Co., Ltd. on 27th Jun. 1989, pp. 26–27),water-soluble calixarenes (Kiichi Takemoto, Mikiji Miyata & KeiichiKimura, “Inclusion Compounds—from Basics to Future Technologies—,”Edition 1, published by Tokyo Kagaku Dozin Co., Ltd. on 27th Jun. 1989,p. 32), etc. It is further believed that water-soluble polymolecularhost compounds difficultly soluble in any organic solvent can be used.It has already been found out that a wide variety of organic compoundsincluding tetrasubstituted benzenes such as durene are included in suchinclusion-complexing agents. Water-soluble cyclophanes are cyclizedcompounds formed, for example, by alternately bonding a plurality of(di)phenylene groups to a plurality of alkylene groups via quaternaryammonium, tertiary sulfonium or monohydroxyammonio-hydroxyethylenegroups, provided that the (di)phenylene groups may be modified withhydrophilic groups such as sulfonic groups either in a free acid form orin a salt form. Water-soluble calixarenes are cyclized compounds formedby alternately bonding a plurality of phenolic rings with hydrophilicgroups such as sulfonic groups either in a free acid form or in a saltform, at their o-positions, to a plurality of methylene groups(generally constituted of 4 to 8 phenolic rings and 4 to 8 methylenegroups), provided that the hydrogen atoms of the phenolic hydroxylgroups may each be substituted with a variety of group.

FIG. 1 is a conceptual cross-sectional view illustrating an example ofreaction vessel in the basic inclusion separator of the presentinvention that may be used in the method of the present invention. Thereaction vessel of FIG. 1 is made up of a squarish U-shaped tube 1. FIG.1 should be considered conceptual because the dimensional ratios and thelike in FIG. 1 do not necessarily represent actual values. Although adiaphragm 2 allowing an aqueous solution of inclusion-complexing agentto pass thereacross is drawn in FIG. 1, it is not necessarily anindispensable element. This reaction vessel is first charged with anaqueous phase 3 of an aqueous solution of inclusion-complexing agent,and then charged with an organic phase 4 of raw material and an organicphase 5 of extraction solvent, followed by stirring. Alternatively,there may be adopted a procedure of charging the reaction vessel withthe aqueous phase 3 and then the organic phase 4 of raw material,stirring at this stage, subsequently charging it with the organic phase5 of extraction solvent, and further stirring. Since the amount of theorganic phase 4 of raw material decreases with an increasing amount ofthe organic phase 5 of extraction solvent as stirring is continued, atleast part of the organic phase 5 of extraction solvent may be withdrawnwith replenishment of the organic phase 4 of raw material if necessary,and fresh extraction solvent may be replenished as needed. Thereafter,the organic phase 5 of extraction solvent is withdrawn as needed, andthe organic phase (oil extract) remaining after removal of theextraction solvent is subjected again or repeatedly to the method of thepresent invention if necessary to heighten the purity of a compound asan object of separation in the oil extract obtained from the organicphase of extraction solvent. Incidentally, the reaction vessels ofinclusion separators of FIGS. 2 and 3 used in the following Examples 1to 9 and 11 to 38 are fundamentally the same as the reaction vessel ofFIG. 1.

FIGS. 4, 5 and 6 are conceptual cross-sectional views illustratinganother example of reaction vessel in the basic inclusion separator ofthe present invention that may be used in the method of the presentinvention. FIG. 4 shows a state of using a raw material higher inspecific gravity than an aqueous phase and an extraction solvent lowerin specific gravity than the aqueous phase. FIG. 5 shows a state ofusing a raw material lower in specific gravity than an aqueous phase andan extraction solvent higher in specific gravity than the aqueous phase.FIG. 6 shows a state of using a raw material and an extraction solventboth higher in specific gravity than an aqueous phase. FIGS. 4, 5 and 6should be considered conceptual because the dimensional ratios and thelike in FIGS. 4, 5 and 6 do not represent the actual values. Althoughdiaphragms 32, 42 and 52 allowing an aqueous solution ofinclusion-complexing agent to pass thereacross are drawn in FIGS. 4, 5and 6, they are not necessarily indispensable elements. In FIGS. 4, 5and 6, numerals 31, 41 and 51 refer to an H-shaped tube (reactionvessel), 33, 43 and 53 to aqueous phases of aqueous solutions ofinclusion-complexing agents, 34, 44 and 54 to organic phases of rawmaterials, and 35, 45 and 55 to organic phases of extraction solvents.Specifically, a reaction vessel made up of an H-shaped tube is desirablyused when the specific gravity of raw material and/or extraction solventis higher than that of the aqueous solution of inclusion-complexingagent, and is operated in substantially the same manner as in the casewhere the reaction vessel of FIG. 1 is used. Incidentally, the reactionvessel of inclusion separator used in the following Example 10 isfundamentally the same as the reaction vessel of FIG. 5.

The number of branch tubes extended vertically in a reaction vessel isnot limited to 2 but may be 3 or more, and is preferably 2 to 8, morepreferably 2 to 6, although it is varied depending on the kind of rawmaterial and the like. A reaction vessel may have at least three branchtubes, so that an aqueous phase of an aqueous solution ofinclusion-complexing agent can have at least three liquid-liquidinterfaces, one of which is an interface with an organic phase of rawmaterial, and the other two or more of which are respective interfaceswith at least two kinds of extraction solvents. In this case, if anydifference(s) in extraction selectivity exists between extractionsolvents that dissociate and extract compounds to be separated from therespective inclusion complexes [see, e.g., “oil extract” columns inTables showing results of Example 3 (n-heptane), Example 5 (n-hexane),Example 6 (mesitylene), Example 8 (diisopropyl ether), Example 9(diisoamyl ether) and Example 10 (dichloromethane)], the purities ofseparated compounds extracted into the respective extraction solventscan be improved by making the most of any such difference(s) inextraction selectivity to decrease the number of repetitions of themethod of the present invention for securing desired purities ofrespective compounds.

Incidentally, when use is made of an extraction solvent lower inspecific gravity than an aqueous solution of inclusion-complexing agentand an extraction solvent higher in specific gravity than the aqueoussolution of inclusion-complexing agent, an H-shaped tube may be usedEven if a plurality of compounds as the components of raw material arenot so different in complex formation constant, the purpose of thepresent invention may possibly be attained if a plurality of extractionsolvents are different in extraction selectivity. In a reaction vesselhaving, e.g., at least four branch tubes, raw material may be put, forexample, into two branch tubes with respectively putting at least twokinds of extraction solvents into the other two or more branch tubes toperform the method of the present invention. Thus, a variety ofembodiments are conceivable.

Each vertical tube of a variety of branched tube such as a U-shaped tubeor an H-shaped tube may be not only circular but also either elliptic orpolygonal such as tetragonal in cross section. The reaction vessel ofthe inclusion separator is not limited to branched tubes, and may be,for example, in the form of a box-like vessel or a cylinder with abottom plate (which may be provided with a ceiling plate) provided witha vertical partition having an aperture at a suitable location thereofto form a plurality of compartments, provided that the aperture may beprovided with a diaphragm if necessary. An aqueous solution ofinclusion-complexing agent is allowed to pass between the compartmentsvia the aperture or the diaphragm.

Although magnetic stirrers were used in Examples, what is essential tostirring for performing the method of the present invention may besufficient stirring at least neighborhoods of liquid-liquid interfaces.Examples of stirring means include stirring with ultrasonic vibration,stirring with shaking (in forward and backward, leftward and rightward,upward and downward, and/or clockwise and counterclockwise directions),stirring with a stirring rod having agitating blades, etc. Wherediaphragms permitting flow thereacross of an aqueous solution ofinclusion-complexing agent are attached to a reaction vessel havingbranch tubes, there may be provided two flow paths making two branchtubes communicate with each other, and the two flow paths may beprovided with respective diaphragms and water jet pumps (preferably onthe downstream sides of the diaphragms). When two water jet pumps in theflow paths making two branch tubes communicate with each other areactuated to form water streams in mutually opposite directions whilesufficiently stirring at least neighborhoods of liquid-liquid interfacesin the branch tubes, the flow of an aqueous solution ofinclusion-complexing agent parted by two diaphragms can be promotedwhile preventing raw material from mixing with extraction solvent due tothe diaphragms to perform the extraction operation more efficiently. Ofcourse, such a technical idea can also apply to a case where thereaction vessel is provided with a plurality of compartments. Forexample, two apertures with short pipes as flow paths may be providedbetween two compartments, and may be provided with diaphragms and waterjet pumps in the same manner as described above. Alternatively, twowater propeller fans, which can send water in opposite directionsthrough apertures formed between two compartments and provided withrespective diaphragms, may be provided in the respective compartments toperform the extraction operation more efficiently.

EXAMPLES

The following Examples will more specifically illustrate the presentinvention, but should not be construed as limiting the scope of theinvention. The compositions of raw material and oil extract wereanalyzed according to capillary gas chromatography. Figures in thefollowing Tables indicate the peak area percentages assigned torespective components based on the total of all peak areas for isomersin raw material and oil extract in each gas chromatogram. The followingTables show changes in the composition of components by inclusioncomplexation and dissociation-extraction. Incidentally, inclusioncomplexation and dissociation-extraction were effected at roomtemperature in all the following Examples.

FIG. 2 is a conceptual schematic cross-sectional view of an inclusionseparator used in Examples 12 and 28, wherein the dimensional ratios andthe like of elements do not represent actual ones. The inside diameterof two tubes in vertical direction (vertical tubes) of a reaction vesselin the form of a squarish U-shaped tube 11 is 28 mm, while the insidediameter of a horizontal tube, which is connected with the verticaltubes having respective bottom plates, is 18 mm. The shortest distancebetween the two vertical tubes is 28 mm, and the height of the verticaltubes is 230 mm. Two magnetic stirrers 18 are installed under the bottomof the reaction vessel of the U-shaped tube 11, while two spinbars 16are placed in the U-shaped tube 11 The U-shaped tube 11 is sealed byputting plugs 17 therein after fed with an aqueous cyclodextrin phase13, an organic phase 14 of raw material and an organic phase 15 ofextraction solvent. Thereafter, the magnetic stirrers 18 are worked torotate the spinbars 16, thereby to effect stirring.

FIG. 3 is a conceptual schematic cross-sectional view of an inclusionseparator used in Examples 1 to 9, 11, 13 to 27 and 29 to 38, whereinthe dimensional ratios and the like of elements do not represent actualones. The inside diameter of two tubes in vertical direction (verticaltubes) of a reaction vessel in the form of a squarish U-shaped tube 21is 23 mm, while the inside diameter of a horizontal tube is 30 mm. Thehorizontal tube having side plates on both ends is connected with thevertical tubes, provided that portions thereof where spinbars 26 areplaced are flat. The shortest distance between the two vertical tubes is60 mm, and the length ranging from the bottom of the reaction vessel ofthe U-shaped tube 21 to the tops of the two vertical tubes is 100 mm. InFIG. 3, a diaphragm 22 made of filter paper or other material is drawn,but is not used in some Examples. Two magnetic stirrers 28 are installedunder the bottom of the reaction vessel of the U-shaped tube 21, whilethe two spinbars 26 are placed in the U-shaped tube 21. The U-shapedtube 21 is sealed by putting plugs 27 therein after fed with an aqueouscyclodextrin phase 23, an organic phase 24 of raw material and anorganic phase 25 of extraction solvent. Thereafter, the magneticstirrers 28 are worked to rotate the spinbars 26, thereby to effectstirring. In Example 7, however, an aqueous cyclodextrin phase 23 and anorganic phase 24 of raw material were placed in the U-shaped tube 21, inwhich plugs 27 were then put, followed by stirring, while an extractionsolvent 26 was subsequently placed in the U-shaped tube 21 after theright plug was pulled out therefrom, followed by reattaching the rightplug and then stirring. Incidentally, the “squarish U-shaped tube” ofFIG. 2 or 3 will hereinafter referred to simply as the “U-shaped tube.”In Example 10 wherein dichloromethane higher in specific gravity than anaqueous cyclodextrin phase was used as extraction solvent, use was madeof an H-shaped tube, which was substantially the same as the U-shapedtube of FIG. 3 except for two vertical tubes alone elongated furtherdownward (the length of tubes ranging from the bottoms of thedownward-elongated tube portions to the tops of the upward-elongatedtube portions is 130 mm). Incidentally, it is a matter of course that anindustrial inclusion separator may be provided with a ceiling plateinstead of plugs, provided that feed and withdrawal of a raw material,an aqueous solution of inclusion-complexing agent and an extractionsolvent are done via pipings.

Example 1

250 ml of a 10 wt. % aqueous solution of a glucosyl-α-cyclodextrinmixture was placed in a U-shaped tube. 15 ml of an about 1:1 mixture ofp-xylene and m-xylene was placed in one vertical tube of the U-shapedtube while 15 ml of n-heptane was placed in the other vertical tube.Stirring was effected in such a manner that the xylene phase did not mixwith the heptane phase. The composition of xylene isomers extracted inthe n-heptane phase after 2 hours is shown in Table 1.

TABLE 1 Raw Material Oil Extract p-Xylene 49.8% 76.3% m-Xylene 50.2%23.7%

Example 2

250 ml of a 10 wt. % aqueous solution of a glucosyl-α-cyclodextrinmixture was placed in a U-shaped tube. 15 ml of an about 1:1 mixture ofp-xylene and m-xylene was placed in one vertical tube of the U-shapedtube while 15 ml of n-heptane was placed in the other vertical tube.Vigorous stirring was effected, provided that the bottom portion of theU-shaped tube was partitioned with filter paper. The composition ofxylene isomers extracted in the n-heptane phase after 1 hour is shown inTable 2.

TABLE 2 Raw Material Oil Extract p-Xylene 49.8% 82.9% m-Xylene 50.2%17.1%

Example 3

250 ml of a 10 wt. % aqueous solution of a glucosyl-α-cyclodextrinmixture was placed in a U-shaped tube. 6 ml of mixed xylene(commercially available product) was placed in one vertical tube of theU-shaped tube while 6 ml of n-heptane was placed in the other verticaltube. Vigorous stirring was effected, provided that the bottom portionof the U-shaped tube was partitioned with filter paper. The compositionof xylene isomers extracted in the n-heptane phase after 2 hours isshown in Table 3.

TABLE 3 Raw Material Oil Extract Ethylbenzene 15.4% 20.7% p-Xylene 18.7%49.6% m-Xylene 44.2% 24.0% o-Xylene 21.7%  5.7%

Example 4

A solution containing 70 g of sodium chloride dissolved in 250 ml of a10 wt. % aqueous solution of a glucosyl-α-cyclodextrin mixture wasplaced in a U-shaped tube. 6 ml of mixed xylene (commercially availableproduct) was placed in one vertical tube of the U-shaped tube while 6 mlof n-hexane was placed in the other vertical tube. Vigorous stirring waseffected, provided that the bottom portion of the U-shaped tube waspartitioned with filter paper. The composition of xylene isomersextracted in the n-hexane phase after 2 hours is shown in Table 4.

TABLE 4 Raw Material Oil Extract Ethylbenzene 15.4% 22.0% p-Xylene 18.7%54.7% m-Xylene 44.2% 20.1% o-Xylene 21.7%  3.2%

Example 5

250 ml of a 10 wt. % aqueous solution of a glucosyl-α- cyclodextrinmixture was placed in a U-shaped tube. 6 ml of mixed xylene(commercially available product) was placed in one vertical tube of theU-shaped tube while 6 ml of n-hexane was placed in the other verticaltube. Stirring was effected in such a manner that the xylene phase didnot mix with the hexane phase. The composition of xylene isomersextracted in the n-hexane phase after 2 hours is shown in Table 5.

TABLE 5 Raw Material Oil Extract Ethylbenzene 15.4% 19.9% p-Xylene 18.7%43.9% m-Xylene 44.2% 26.8% o-Xylene 21.7%  9.4%

Example 6

250 ml of a 10 wt. % aqueous solution of a glucosyl-α-cyclodextrinmixture was placed in a U-shaped tube. 6 ml of mixed xylene(commercially available product) was placed in one vertical tube of theU-shaped tube while 6 ml of mesitylene was placed in the other verticaltube. Stirring was effected in such a manner that the xylene phase didnot mix with the mesitylene phase. The composition of xylene isomersextracted in the mesitylene phase after 2 hours is shown in Table 6.

TABLE 6 Raw Material Oil Extract Ethylbenzene 15.4% 19.2% p-Xylene 18.7%42.4% m-Xylene 44.2% 28.7% o-Xylene 21.7%  9.7%

Example 7

250 ml of a 10 wt. % aqueous solution of a glucosyl-α-cyclodextrinmixture was placed in a U-shaped tube. 10 ml of mixed xylene(commercially available product) was placed in one vertical tube of theU-shaped tube. Vigorous stirring was effected, provided that the bottomportion of the U-shaped tube was partitioned with filter paper. After 20minutes, 5 ml of diethyl ether was added to the other vertical tube ofthe U-shaped tube, and both spinbars were revolved to effect 5 secondsof vigorous stirring. Thereafter, the liquids were allowed to stand(about 30–60 seconds) until the aqueous cyclodextrin phase was separatedfrom the ether phase. The ether phase was recovered. The composition ofxylene isomers extracted in the ether phase is shown in Table 7.Incidentally, initial 20 minutes of stirring was an operation ofentrapment into the aqueous phase from mixed xylene through complexformation, while subsequent 5 seconds of stirring was an operation ofextracting substances migrated to the aqueous phase into the ether phasethrough complex dissociation. The short stirring time of 5 seconds wasdue to a difficulty in phase separation between the aqueous phase andthe ether phase if stirred for a long time, because diethyl ether is alittle soluble in water.

TABLE 7 Raw Material Oil Extract Ethylbenzene 15.4% 20.8% p-Xylene 18.7%50.2% m-Xylene 44.2% 24.6% o-Xylene 21.7%  4.5%

Example 8

250 ml of a 10 wt. % aqueous solution of a glucosyl-α-cyclodextrinmixture was placed in a U-shaped tube. 10 ml of mixed xylene(commercially available product) was placed in one vertical tube of theU-shaped tube while 10 ml of diisopropyl ether was placed in the othervertical tube. Vigorous stirring was effected with both spinbars,provided that the bottom portion of the U-shaped tube was partitionedwith filter paper. The composition of xylene isomers extracted in thediisopropyl ether phase after 30 minutes is shown in Table 8.

TABLE 8 Raw Material Oil Extract Ethylbenzene 15.4% 20.0% p-Xylene 18.7%46.7% m-Xylene 44.2% 24.4% o-Xylene 21.7%  8.9%

Example 9

260 ml of a 10 wt. % aqueous solution of a glucosyl-α-cyclodextrinmixture was placed in a U-shaped tube. 10 ml of mixed xylene(commercially available product) was placed in one vertical tube of theU-shaped tube while 10 ml of diisoamyl ether was placed in the othervertical tube. Vigorous stirring was effected, provided that the bottomportion of the U-shaped tube was partitioned with filter paper. Thecomposition of xylene isomers extracted in the diisoamyl ether phaseafter 30 minutes is shown in Table 9.

TABLE 9 Raw Material Oil Extract Ethylbenzene 15.4% 20.4% p-Xylene 18.7%41.5% m-Xylene 44.2% 26.3% o-Xylene 21.7% 11.8%

Example 10

250 ml of a 10 wt. % aqueous solution of a glucosyl-α-cyclodextrinmixture was placed in an H-shaped tube. 10 ml of mixed xylene(commercially available product) was placed in one vertical tube of theH-shaped tube while 5 ml of dichloromethane was placed in the othervertical tube. Vigorous stirring was effected, provided that thehorizontal pipe portion of the H-shaped tube was partitioned with filterpaper. The composition of xylene isomers extracted in thedichioromethane phase after 1 hour is shown in Table 10.

TABLE 10 Raw Material Oil Extract Ethylbenzene 15.4% 21.0% p-Xylene18.7% 52.3% m-Xylene 44.2% 22.2% o-Xylene 21.7%  4.5%

Example 11

250 ml of a 10 wt. % aqueous solution of a maltosyl-β-cyclodextrinmixture was placed in a U-shaped tube. 20 ml of mixed xylene(commercially available product) was placed in one vertical tube of theU-shaped tube while 20 ml of n-heptane was placed in the other verticaltube. Stirring was effected in such a manner that the xylene phase didnot mix with the heptane phase. The composition of xylene isomersextracted in the n-heptane phase after 1 hour is shown in Table 11.

TABLE 11 Raw Material Oil Extract Ethylbenzene 15.5% 13.0% p-Xylene18.6% 17.8% m-Xylene 43.2% 30.9% o-Xylene 22.7% 38.2%

Example 12

100 ml of a 10 wt. % aqueous solution of 2,6-dimethyl-α-cyclodextrin wasplaced in a U-shaped tube. 5 ml of mixed xylene (commercially availableproduct) was placed in one vertical tube of the U-shaped tube while 5 mlof n-heptane was placed in the other vertical tube. Stirring waseffected in such a manner that the xylene phase did not mix with theheptane phase. The composition of xylene isomers extracted in then-heptane phase after 1 hour is shown in Table 12.

TABLE 12 Raw Material Oil Extract Ethylbenzene 15.4% 26.0% p-Xylene18.7% 17.5% m-Xylene 44.2% 42.7% o-Xylene 21.7% 13.8%

Example 13

250 ml of a 10 wt. % aqueous solution of a glucosyl-α-cyclodextrinmixture was placed in a U-shaped tube. 6 ml of a mixture ofo-nitrotoluene, m-nitrotoluene and p-nitrotoluene was placed in onevertical tube of the U-shaped tube while 6 ml of n-heptane was placed inthe other vertical tube. Vigorous stirring was effected, provided thatthe bottom portion of the U-shaped tube was partitioned with filterpaper. The composition of nitrotoluene isomers extracted in then-heptane phase after 2 hours is shown in Table 13.

TABLE 13 Raw Material Oil Extract o-Nitrotoluene 34.6% 13.6%m-Nitrotoluene 33.0% 27.7% p-Nitrotoluene 32.4% 58.7%

Example 14

250 ml of a 10 wt. % aqueous solution of a glucosyl-α-cyclodextrinmixture was placed in a U-shaped tube. 1 ml of a mixture ofo-chlorotoluene, m-chlorotoluene and p-chlorotoluene was placed in onevertical tube of the U-shaped tube while 10 ml of n-heptane was placedin the other vertical tube. Vigorous stirring was effected, providedthat the bottom portion of the U-shaped tube was partitioned with filterpaper. The composition of chlorotoluene isomers extracted in then-heptane phase after 2 hours is shown in Table 14.

TABLE 14 Raw Material Oil Extract o-Chlorotoluene 33.5% 17.1%m-Chlorotoluene 33.0% 29.5% p-Chlorotoluene 33.5% 53.3%

Example 15

250 ml of a 10 wt. % aqueous solution of a glucosyl-α-cyclodextrinmixture was placed in a U-shaped tube. 0.5 ml of a mixture ofo-chlorobenzotrifluoride, m-chlorobenzotrifluoride andp-chlorobenzotrifluoride was placed in one vertical tube of the U-shapedtube while 5 ml of n-heptane was placed in the other vertical tube.Vigorous stirring was effected, provided that the bottom portion of theU-shaped tube was partitioned with filter paper. The composition ofchlorobenzotrifluoride isomers extracted in the n-heptane phase after 2hours is shown in Table 15.

TABLE 15 Raw Material Oil Extract o-Chlorobenzotrifluoride 33.2% 31.8%m-Chlorobenzotrifluoride 29.6% 14.1% p-Chlorobenzotrifluoride 37.1%54.1%

Example 16

250 ml of a 10 wt. % aqueous solution of a glucosyl-α-cyclodextrinmixture was placed in a U-shaped tube. 1.8 ml of a mixture of 3trimethylbenzene isomers, i.e., mesitylene, pseudocumene andhemimellitene, was placed in one vertical tube of the U-shaped tubewhile 5 ml of n-heptane was placed in the other vertical tube. Vigorousstirring was effected, provided that the bottom portion of the U-shapedtube was partitioned with filter paper. The composition oftrimethylbenzene isomers extracted in the n-heptane phase after 3 hoursis shown in Table 16.

TABLE 16 Raw Material Oil Extract Mesitylene 33.0% 16.2% Pseudocumene34.0% 17.9% Hemimellitene 33.0% 65.9%

Example 17

250 ml of a 10 wt. % aqueous solution of a maltosyl-62 -cyclodextrinmixture was placed in a U-shaped tube. 1.8 ml of a mixture of 3trimethylbenzene isomers, i.e., mesitylene, pseudocumene andhemimellitene, was placed in one vertical tube of the U-shaped tubewhile 5 ml of n-heptane was placed in the other vertical tube. Vigorousstirring was effected, provided that the bottom portion of the U-shapedtube was partitioned with filter paper. The composition oftrimethylbenzene isomers extracted in the n-heptane phase after 3 hoursis shown in Table 17.

TABLE 17 Raw Material Oil Extract Mesitylene 33.0% 18.4% Pseudocumene34.0% 59.5% Hemimellitene 33.0% 22.1%

Example 18

250 ml of a 10 wt. % aqueous solution of a glucosyl-α-cyclodextrinmixture was placed in a U-shaped tube. 6 ml of a mixture of 3trichlorobenzene isomers, i.e., 1,3,5-trichlorobenzene,1,2,4-trichlorobenzene and 1,2,3-trichlorobenzene, was placed in onevertical tube of the U-shaped tube while 6 ml of n-heptane was placed inthe other vertical tube. Vigorous stirring was effected, provided thatthe bottom portion of the U-shaped tube was partitioned with filterpaper. The composition of trichlorobenzene isomers extracted in then-heptane phase after 1 hour is shown in Table 18.

TABLE 18 Raw Material Oil Extract 1,3,5-Trichlorobenzene 34.3% 23.8%1,2,4-Trichlorobenzene 33.0% 21.3% 1,2,3-Trichlorobenzene 32.7% 54.9%

Example 19

250 ml of a 10 wt. % aqueous solution of a glucosyl-α-cyclodextrinmixture was placed in a U-shaped tube. 6 ml of a n-heptane solution of 3dimethylphenol isomers, i.e., 2,3-dimethylphenol, 3,4-dimethylphenol and3,5-dimethylphenol, was placed in one vertical tube of the U-shaped tubewhile 6 ml of n-heptane was placed in the other vertical tube. Vigorousstirring was effected, provided that the bottom portion of the U-shapedtube was partitioned with filter paper. The composition ofdimethylphenol isomers extracted in the n-heptane phase after 2 hours isshown in Table 19.

TABLE 19 Raw Material Oil Extract 3,5-Dimethylphenol 31.4% 23.2%2,3-Dimethylphenol 34.5% 51.5% 3,4-Dimethylphenol 34.1% 25.3%

Example 20

250 ml of a 10 wt. % aqueous solution of a glucosyl-α-cyclodextrinmixture was placed in a U-shaped tube. 2 ml of a mixture of 3nitroxylene isomers, i.e., 2-nitro-m-xylene, 4-nitro-m-xylene and5-nitro-m-xylene, was placed in one vertical tube of the U-shaped tubewhile 5 ml of n-heptane was placed in the other vertical tube. Vigorousstirring was effected, provided that the bottom portion of the U-shapedtube was partitioned with filter paper. The composition of nitroxyleneisomers extracted in the n-heptane phase after 2 hours is shown in Table20.

TABLE 20 Raw Material Oil Extract 2-Nitro-m-xylene 34.8% 72.0%4-Nitro-m-xylene 32.5%  9.5% 5-Nitro-m-xylene 32.7% 18.6%

Example 21

250 ml of a 10 wt. % aqueous solution of a glucosyl-α-cyclodextrinmixture was placed in a U-shaped tube. 0.5 ml of a mixture of1-methylnaphthalene and 2-methylnaphthalene was placed in one verticaltube of the U-shaped tube while 3 ml of n-heptane was placed in theother vertical tube. Vigorous stirring was effected, provided that thebottom portion of the U-shaped tube was partitioned with filter paper.The composition of methylnaphthalene isomers extracted in the n-heptanephase after 2 hours is shown in Table 21.

TABLE 21 Raw Material Oil Extract 1-Methylnaphthalene 50.4%  7.8%2-Methylnaphthalene 49.6% 92.2%

Example 22

250 ml of a 10 wt. % aqueous solution of a glucosyl-α-cyclodextrinmixture was placed in a U-shaped tube. 0.5 ml of a dimethylnaphthalenemixture (commercially available product) was placed in one vertical tubeof the U-shaped tube while 3 ml of n-heptane was placed in the othervertical tube. Vigorous starring was effected, provided that the bottomportion of the U shaped tube was partitioned with filter paper. Thecomposition of dimethylnaphthalene isomers extracted in the n-heptanephase after 90 minutes is shown in Table 22.

TABLE 22 Raw Material Oil Extract 2,6-Dimethylnaphthalene 10.6% 42.2%2,7-Dimethylnaphthalene 13.5%  4.0% Other Dimethylnaphthalenes 75.9%53.8%

Example 23

250 ml of a 10 wt. % aqueous solution of a maltosyl-β-cyclodextrinmixture was placed in a U-shaped tube. 1 ml of a mixture of2,6-diisopropylnaphthalene and 2,7-diisopropylnaphthalene was placed inone vertical tube of the U-shaped tube while 5 ml of n-heptane wasplaced in the other vertical tube. Vigorous stirring was effected,provided that the bottom portion of the U-shaped tube was partitionedwith filter paper. The composition of diisopropylnaphthalene isomersextracted in the n-heptane phase after 2 hours is shown in Table 23.

TABLE 23 Raw Material Oil Extract 2,6-Diisopropylnaphthalene 49.2% 68.2%2,7-Diisopropylnaphthalene 50.8% 31.8%

Example 24

250 ml of a 10 wt. % aqueous solution of a glucosyl-α-cyclodextrinmixture was placed in a U-shaped tube. 2 ml of a mixture of2-methylquinoline and 8-methylquinoline was placed in one vertical tubeof the U-shaped tube while 10 ml of n-heptane was placed in the othervertical tube. Vigorous stirring was effected, provided that the bottomportion of the U-shaped tube was partitioned with filter paper. Thecomposition of methylquinoline isomers extracted in the n-heptane phaseafter 1 hour is shown in Table 24.

TABLE 24 Raw Material Oil Extract 2-Methylquinoline 48.8% 59.8%8-Methylquinoline 51.2% 40.2%

Example 25

250 ml of a 10 wt. % aqueous solution of a glucosyl-α-cyclodextrinmixture was placed in a U-shaped tube. 2 ml of a mixture of7-methylquinoline and 5-methylquinoline was placed in one vertical tubeof the U-shaped tube while 10 ml of n-heptane was placed in the othervertical tube. Vigorous stirring was effected, provided that the bottomportion of the U-shaped tube was partitioned with filter paper. Thecomposition of methylquinoline isomers extracted in the n-heptane phaseafter 1 hour is shown in Table 25.

TABLE 25 Raw Material Oil Extract 7-Methylquinoline 81.0% 86.9%5-Methylquinoline 19.0% 13.1%

Example 26

250 ml of a 20 wt. % aqueous solution of a glucosyl-α-cyclodextrinmixture was placed in a U-shaped tube. 15 ml of an about 1:1 mixture ofp-xylene and m-xylene was placed in one vertical tube of the U-shapedtube while 10 ml of n-hexane was placed in the other vertical tube.Vigorous stirring was effected, provided that the bottom portion of theU-shaped tube was partitioned with filter paper. The composition ofxylene isomers extracted in the n-hexane phase after 1 hour is shown inTable 26.

TABLE 26 Raw Material Oil Extract p-Xylene 49.8% 83.2% m-Xylene 50.2%16.8%

Example 27

250 ml of a 20 wt. % aqueous solution of a glucosyl-α-cyclodextrinmixture was placed in a U-shaped tube. 30 ml of an about 1:1 mixture ofp-xylene and m-xylene was placed in one vertical tube of the U-shapedtube while 40 ml of n-pentane was placed in the other vertical tube.Vigorous stirring was effected, provided that the bottom portion of theU-shaped tube was partitioned with filter paper. After 30 minutes,stirring on the n-pentane phase side was stopped. When the aqueouscyclodextrin phase was separated from the n-pentane phase, about 20 mlof the n-pentane solution of the n-pentane phase was transferred to adistillation apparatus. Thereafter, stirring was continued in theU-shaped tube. On the other hand, extracted xylenes were concentratedwith the distillation apparatus, while n-pentane vaporized throughdistillation was cooled and liquefied, and then returned back to then-pentane phase in the U-shaped tube. After about 5 minutes, the sameprocedure as described above was performed. The foregoing procedure wasrepeated. The composition of xylene isomers concentrated in thedistillation apparatus after 6 hours is shown in Table 27.

TABLE 27 Raw Material Oil Extract p-Xylene 49.8% 80.8% m-Xylene 50.2%19.2%

Example 28

100 ml of a 10 wt. % aqueous solution of α-cyclodextrin dissolved inwater containing 10 wt. % sodium hydroxide was placed in a U-shapedtube. 20 ml of mixed xylene (commercially available product) was placedin one vertical tube of the U-shaped tube while 20 ml of n-heptane wasplaced in the other vertical tube. Stirring was effected in such amanner that the xylene phase did not mix with the heptane phase. Thecomposition of xylene isomers extracted in the n-heptane phase after 2hours is shown in

TABLE 28 Raw Material Oil Extract Ethylbenzene 15.5% 20.4% p-Xylene18.6% 23.3% m-Xylene 43.2% 42.8% o-Xylene 22.7% 13.5%

Example 29

230 ml of a 10 wt. % aqueous solution of a glucosyl-α-cyclodextrinmixture was placed in a U-shaped tube. 15 ml of an about 1:1 mixture ofp-xylene and m-xylene was placed in one vertical tube of the U-shapedtube while 10 ml of n-hexane was placed in the other vertical tube.Vigorous stirring was effected, provided that the bottom portion of theU-shaped tube was partitioned with a rayon nonwoven fabric. Thecomposition of xylene isomers extracted in the n-hexane phase after 1hour is shown in Table 29.

TABLE 29 Raw Material Oil Extract p-Xylene 49.9% 71.0% m-Xylene 50.1%29.0%

Example 30

230 ml of a 10 wt. % aqueous solution of a glucosyl-α-cyclodextrinmixture was placed in a U-shaped tube. 15 ml of an about 1:1 mixture ofp-xylene and m-xylene was placed in one vertical tube of the U-shapedtube while 10 ml of n-hexane was placed in the other vertical tube.Vigorous stirring was effected, provided that the bottom portion of theU-shaped tube was partitioned with a glass fiber filter. The compositionof xylene isomers extracted in the n-hexane phase after 1 hour is shownin Table 30.

TABLE 30 Raw Material Oil Extract p-Xylene 49.9% 83.4% m-Xylene 50.1%16.6%

Example 31

230 ml of a 10 wt. % aqueous solution of a glucosyl-α-cyclodextrinmixture was placed in a U-shaped tube. 15 ml of an about 1:1 mixture ofp-xylene and m-xylene was placed in one vertical tube of the U-shapedtube while 10 ml of n-heptane was placed in the other vertical tube.Vigorous stirring was effected, provided that the bottom portion of theU-shaped tube was partitioned with a nylon net filter. The compositionof xylene isomers extracted in the n-heptane phase after 1 hour is shownin Table 31.

TABLE 31 Raw Material Oil Extract p-Xylene 50.0% 82.2% m-Xylene 50.0%17.8%

Example 32

230 ml of a 10 wt. % aqueous solution of a glucosyl-α-cyclodextrinmixture was placed in a U-shaped tube. 15 ml of an about 1:1 mixture ofp-xylene and m-xylene was placed in one vertical tube of the U-shapedtube while 10 ml of n-heptane was placed in the other vertical tube.Vigorous stirring was effected, provided that the bottom portion of theU-shaped tube was partitioned with a filter portion of glass filtrationapparatus. The composition of xylene isomers extracted in the n-heptanephase after 1 hour is shown in Table 32.

TABLE 32 Raw Material Oil Extract p-Xylene 50.0% 81.2% m-Xylene 50.0%18.8%

Example 33

230 ml of a 10 wt. % aqueous solution of a glucosyl-α-cyclodextrinmixture was placed in a U-shaped tube. 10 ml of an about 1:1 mixture ofp-xylene and m-xylene was placed in one vertical tube of the U-shapedtube while 10 ml of n-heptane was placed in the other vertical tube.Vigorous stirring was effected, provided that the bottom portion of theU-shaped tube was partitioned with a stainless steel net. Thecomposition of xylene extracted in the n-heptane phase after 1 hour isshown in Table 33.

TABLE 33 Raw Material Oil Extract p-Xylene 50.0% 77.9% m-Xylene 50.0%22.1%

Example 34

250 ml of a 10 wt. % aqueous solution of a glucosyl-α-cyclodextrinmixture was placed in a U-shaped tube. 10 ml of an about 1:1 mixture ofp-xylene and m-xylene was placed in one vertical tube of the U-shapedtube while 10 ml of n-heptane was placed in the other vertical tube.Vigorous stirring was effected, provided that the bottom portion of theU-shaped tube was partitioned with a silk screen The composition ofxylene isomers extracted in the n-heptane phase after 1 hour is shown inTable 34.

TABLE 34 Raw Material Oil Extract p-Xylene 49.9% 70.2% m-Xylene 50.1%29.8%

Example 35

230 ml of a 10 wt. % aqueous solution of a glucosyl-α-cyclodextrinmixture containing 69 g of potassium chloride was placed in a U-shapedtube. 10 ml of an about 1:1 mixture of p-xylene and m-xylene was placedin one vertical tube of the U-shaped tube while 10 ml of n-heptane wasplaced in the other vertical tube. Vigorous stirring was effected,provided that the bottom portion of the U-shaped tube was partitionedwith a nylon net filter. The composition of xylene isomers extracted inthe n-heptane phase after 1 hour is shown in Table 35.

TABLE 35 Raw Material Oil Extract p-Xylene 50.0% 88.1% m-Xylene 50.0%11.9%

Example 36

230 ml of a 10 wt. % aqueous solution of a glucosyl-α-cyclodextrinmixture containing 83 g of sodium sulfate was placed in a U-shaped tube.10 ml of an about 1:1 mixture of p-xylene and m-xylene was placed in onevertical tube of the U-shaped tube while 10 ml of n-heptane was placedin the other vertical tube. Vigorous stirring was effected, providedthat the bottom portion of the U-shaped tube was partitioned with anylon net filter. The composition of xylene isomers extracted in then-heptane phase after 1 hour is shown in Table 36.

TABLE 36 Raw Material Oil Extract p-Xylene 50.0% 87.5% m-Xylene 50.0%12.5%

Example 37

250 ml of a 10 wt. % aqueous solution of a glucosyl-α-cyclodextrinmixture was placed in a U-shaped tube. 10 ml of an about 1:1 mixture of(1S)-(−)-α-pinene and (1R)-(+)-α-pinene was placed in one vertical tubeof the U-shaped tube while 10 ml of n-heptane was placed in the othervertical tube. Vigorous stirring was effected, provided that the bottomportion of the U-shaped tube was partitioned with filter paper. Thecomposition of a-pinene isomers extracted in the n-heptane phase after90 minutes is shown in Table 37.

TABLE 37 Raw Material Oil Extract (1S)-(−)-α-Pinene 49.5% 69.5%(1R)-(+)-α-Pinene 50.5% 30.5%

Example 38

250 ml of a 10 wt. % aqueous solution of a glucosyl-α-cyclodextrinmixture was placed in a U-shaped tube. 10 ml of (±)-limonene was placedin one vertical tube of the U-shaped tube while 10 ml of n-heptane wasplaced in the other vertical tube. Vigorous stirring was effected,provided that the bottom portion of the U-shaped tube was partitionedwith filter paper. The composition of limonene isomers extracted in then-heptane phase after 90 minutes is shown in Table 38.

TABLE 38 Raw Material Oil Extract (S)-(−)-Limonene 49.8% 42.2%(R)-(+)-Limonene 50.2% 57.8%

INDUSTRIAL APPLICABILITY

An operation of selectively inclusion-complexing a compound by anaqueous solution of cyclodextrin and an operation of dissociating andrecovering the compound selectively entrapped by the aqueous solution ofcyclodextrin from the cyclodextrin have heretofore been performedseparately. According to the present invention, these operations can beconsecutively performed to make the whole separation process veryefficient.

What is claimed is:
 1. A continuous and selective inclusion separationmethod, said method comprising the following steps: a) providing areaction system comprising: i) a first organic phase comprising a rawmaterial comprising at least one compound to be separated; ii) a secondorganic phase comprising at least one extraction solvent; iii) anaqueous phase comprising at least one inclusion-complexing agent, saidaqueous phase simultaneously being in contact with both said firstorganic phase and said second organic phase so that a firstliquid-liquid interface is formed between said first organic phase andsaid aqueous phase and simultaneously a second liquid-liquid interfaceis formed between said second organic phase and said aqueous phase; andiv) a diaphragm provided in said aqueous phase and distanced from bothsaid first and second liquid-liquid interfaces; b) stirring at least apart of the first organic phase and at least a part of the aqueous phaseto form oil droplets comprising the raw material in the aqueous phasewherein there is formed at least one inclusion complex comprising acomplex of; i) said at least one compound; and ii) said at least oneinclusion-complexing agent; c) stirring at least a part of the secondorganic phase and at least a part of the aqueous phase to form oildroplets comprising said at least one compound separated from said atleast one inclusion complex; wherein said diaphragm is permeable to saidcomplex of said at least one compound and said at least oneinclusion-complexing agent, and, upon said stirring, said diaphragmprevents said oil droplets comprising the raw material in the aqueousphase comprising at least one inclusion complex from mixing with saidoil droplets comprising said at least one compound separated ftom saidat least one inclusion complex.
 2. A continuous and selective inclusionseparation method as claimed in 1, wherein said inclusion-complexingagent is at least one cyclodextrin.
 3. A continuous and selectiveinchision separation method as claimed in 1, wherein said raw materialcontaining at least one compound to be separated is a raw materialselected from the group consisting of indole-conraining mixtures,disubstituted beuzene isomer mixtures, trisubstituted benzene isomermixtures, 2-methylquinoline-containing hydrocarbon oils,7-methylquinoline-containing mixtures,2,6-diisopropylnaphthalene-containing mixtures,2-methylnaphthalene-containing mixtures,2,6-dimethylnaphthalene-containing mixtures, and optical isomer mixturesof pinene. limonene, menthol, and mandelic acid esters.
 4. A continuousand selective inclusion separation method as claimed in
 1. wherein atleast part of a solution as the second organic phase containing acompound extracted thereinto as an object of separation is withdrawn anddistilled to concentrate said compound, and the organic solventseparaled by distillation is returned back to the reaction system andreused as the extraction solvent.